Autosomal Dominant Rhegmatogenous Retinal Detachment Associated with an Arg453Ter Mutation in theCOL2A1Gene

Abstract

In two large families with RRD, linkage was found at the COL2A1 locus. In one of these families an Arg453Ter mutation was identified, which is surprising, because all predominantly ocular Stickler syndrome cases until now have been associated with protein-truncating mutations in exon 2, an exon subject to alternative splicing. In contrast, the Arg453Ter mutation and other protein-truncating mutations in the helical domain of COL2A1 have been associated until now with classic Stickler syndrome.

Autosomal dominant rhegmatogenous retinal detachment—clinical appearance and surgical outcome

“…Only 1 of 21 affected eyes showed a juvenile cataract (individual BII-10). However, none of the remaining family members showed classic ocular or systemic features associated with Wagner disease, Stickler syndrome or other connective tissue disorders that might be associated with RRD, as detailed elsewhere [5]. We found lattice degeneration in some family members, but not in any subject with RRD.…”

“…In both of the families in our study, the underlying genetic defect was located in the chromosomal region containing the COL2A1 gene, and in one of the families (family B), a protein-truncating mutation was found in the middle of the helical domain of the COL2A1 gene, a type of mutation generally found in patients with classic Stickler syndrome [5]. To date, there is no clear explanation for this finding.…”

“…DNA linkage analysis in all family members had shown that the RRD phenotype in both families cosegregated with the 12q13 region containing the COL2A1 gene. In family A no mutation could be identified in the protein coding exons of COL2A1; in family B, an Arg435Ter mutation located in the triple helical domain of the COL2A1 gene was found [5].…”

“…Although an atypical ocular form of Stickler syndrome cannot be excluded, predominantly ocular Stickler syndromes have been associated with COL2A1 exon 2 mutations [16]. In contrast, the genetic defect found in family B was an exon 30 mutation [5].…”

“…In neither family were the classic ocular and systemic features of complex hereditary vitreoretinopathies such as Wagner disease and Stickler syndrome recorded, as described elsewhere [5].…”